晚期 EGFR 突变 NSCLC 对奥西替尼的耐药性：组织和液体活检分子基因分型的前瞻性研究。
Resistance to osimertinib in advanced EGFR-mutated NSCLC: a prospective study of molecular genotyping on tissue and liquid biopsies.
发表日期：2023 Nov 08
作者：
A Leonetti, M Verzè, R Minari, F Perrone, L Gnetti, P Bordi, M Pluchino, R Nizzoli, C Azzoni, L Bottarelli, C A M Lagrasta, G Mazzaschi, S Buti, D Gasparro, A Cosenza, L Ferri, M Majori, M De Filippo, L Ampollini, S La Monica, R Alfieri, E M Silini, M Tiseo
来源：
BRITISH JOURNAL OF CANCER
摘要：
晚期 EGFR 突变非小细胞肺癌 (NSCLC) 对奥希替尼的耐药性对临床医生在分子诊断和后续治疗意义方面构成了重大挑战。这是一项前瞻性单中心研究，主要目的是描述耐药机制在一线和二线治疗的晚期 EGFR 突变 NSCLC 患者中使用奥希替尼。对配对的组织活检和血浆样本进行了下一代测序分析。对组织和血浆之间进行一致性分析。纳入了 65 例接受奥希替尼一线治疗 (n = 56) 或二线治疗 (n = 9) 的晚期 EGFR 突变 NSCLC 患者。我们成功地分别对 65.5% 和 89.7% 经历奥希替尼进展的患者进行了组织和液体活检。在 25 名进展后样本中，80% 的患者发现了获得性耐药机制，其中最常发现的是 MET 扩增 (n = 8)、EGFR C797S (n = 3) 和 SCLC 转化 (n = 2)。组织和血浆中 EGFR 激活突变和分子耐药机制的平均一致性率分别为 87.5% 和 22.7%。对奥希替尼的耐药性被证明具有高度异质性，其中 MET 扩增是主要机制。血浆基因分型是一种相关的补充工具，可以整合组织分析来研究耐药机制。© 2023。作者，获得 Springer Nature Limited 的独家许可。
Resistance to osimertinib in advanced EGFR-mutated non-small cell lung cancer (NSCLC) constitutes a significant challenge for clinicians either in terms of molecular diagnosis and subsequent therapeutic implications.This is a prospective single-centre study with the primary objective of characterising resistance mechanisms to osimertinib in advanced EGFR-mutated NSCLC patients treated both in first- and in second-line. Next-Generation Sequencing analysis was conducted on paired tissue biopsies and plasma samples. A concordance analysis between tissue and plasma was performed.Sixty-five advanced EGFR-mutated NSCLC patients treated with osimertinib in first- (n = 56) or in second-line (n = 9) were included. We managed to perform tissue and liquid biopsies in 65.5% and 89.7% of patients who experienced osimertinib progression, respectively. Acquired resistance mechanisms were identified in 80% of 25 patients with post-progression samples, with MET amplification (n = 8), EGFR C797S (n = 3), and SCLC transformation (n = 2) the most frequently identified. The mean concordance rates between tissue and plasma for the EGFR activating mutation and for the molecular resistance mechanisms were 87.5% and 22.7%, respectively.Resistance to osimertinib demonstrated to be highly heterogeneous, with MET amplification the main mechanism. Plasma genotyping is a relevant complementary tool which might integrate tissue analysis for the study of resistance mechanisms.© 2023. The Author(s), under exclusive licence to Springer Nature Limited.